Association of ACE2 and TMPRSS2 genes variants with disease severity and most important biomarkers in COVID-19 patients in Bosnia and Herzegovina.

AIM: To assess the association of single nucleotide polymorphisms (SNPs) in the ACE2 and TMPRSS2 genes with COVID-19 severity and key biomarkers. METHODS: The study involved 750 COVID-19 patients from Bosnia and Herzegovina, divided into three groups: mild, moderate, and severe cases. Genetic variations within the ACE2 (rs2285666) and TMPRSS2 (rs2070788) genes were examined with real-time polymerase chain reaction. Biochemical markers were determined with standard procedures. RESULTS: There was a significant difference in the rs2070788 genotype distribution between patients with mild and moderate symptoms, but not between other groups. For the rs2285666 polymorphism, no significant difference in genotype distribution was found. In patients with mild symptoms, carriers of the GG genotype of rs2070788 had significantly higher total bilirubin levels than carriers of the AA genotype. Similarly, carriers of the TT genotype of rs2285666 had significantly higher activated partial thromboplastin time and international normalized ratio, and lower lactate dehydrogenase levels compared with the CC genotype. Among patients with severe symptoms, carriers of the GG genotype showed significantly higher potassium levels than carriers of the AA genotype, while carriers of the TT genotype showed significantly higher erythrocyte count as well as hemoglobin and hematocrit levels compared with the CC genotype. CONCLUSION: This study highlights the role of genetic factors, particularly SNPs in the ACE2 and TMPRSS2 genes, in determining COVID-19 severity, aiding patient risk assessment and prognosis.

Effect of Cigarette Smoking on Haematological Parameters in Healthy Population.

OBJECTIVE: Tobacco cigarette smoking is one of the major leading causes of death throughout the world. Smoking has both acute and chronic effect on haematological parameters. The aim of the present study was to assess the extent of adverse effects of cigarette smoking on biochemical characteristics in healthy smokers. SUBJECTS AND METHOD: One hundred and fifty six subjects participated in this study, 56 smokers and 100 non-smokers. The smokers were regularly consuming 10-20 cigarettes per day for at least 3 years. Complete blood cell count was analyzed by CELL-DYN 3700 fully automatic haematological analyzer. RESULTS: The smokers had significantly higher levels of white blood cell (p<0,001), hemoglobin (p=0,042), mean corpuscular volume (p=0,001) and mean corpuscular hemoglobin concentration (p<0,001). All other measured parameters did not differ significantly. Cigarette smoking caused a significant increase (p<0,001) in red blood cells, white blood cells (p=0,040), hemoglobin (p<0,001), hematocrit (p=0,047) and mean corpuscular hemoglobin (p<0,001) in males in comparison to female smokers. CONCLUSION: In conclusion, our study showed that continuous cigarette smoking has severe adverse effects on haematological parameters (e.g., hemoglobin, white blood cells count, mean corpuscular volume, mean corpuscular hemoglobin concentration, red blood cells count, hematocrit) and these alterations might be associated with a greater risk for developing atherosclerosis, polycythemia vera, chronic obstructive pulmonary disease and/or cardiovascular diseases.

Public Health Dimensions of CVD Prevention and Control - Global Perspectives and Current Situation in the Federation of BiH.

Background: CVD remains a leading cause of death in Europe and worldwide accounting for 3.9 million deaths each year in Europe alone. Even with well-known risk factors and the current standards of health care, improvement of health and quality of life of CVD patients are still remains one of the biggest public health challenges we must overcome. Objective: The aim of this narrative review is to provide a brief overview of the recent and relevant documents of good practice in prevention, diagnostic and therapeutic approaches of Cardiovascular diseases that should be consider as milestones for the health authorities in the Federation of BiH. Cardiovascular diseases stil represent a worldwide public health problem, with some new dimensions caused by challenges caused through pandemic of COVID-19. The wellknown cardiovascular risk factors require new and more efficient public health approaches to the prevention and control. Conclusion: Due to the recently developed cardiovascular guidelines that were made by the European Society of Cardiology and World Heart Federation, key priority for health authorities should be is to update the existing CVD guidelines in the Federation of BiH in accordance with the international good practice.

Effect of Diabetic Neuropathy on Reparative Ability and Immune Response System.

The effects of diabetes can be divided into short, medium and long term and various human organ systems can be effected. The present study aimed to determine how much the duration of diabetes mellitus (DM) affect the reparative ability of the body, immune response and the development of DM complications. Interleukin 1-ß (IL-1ß) and Interleukin 6 (IL-6) were monitored as specific indicators of inflammatory reaction and C-reactive protein (CRP), leukocyte count (WBC) and sedimentation rate (ESR) as general markers of inflammatory reaction. Tumour necrosis factor α (TNF-α) and transforming growth factor ß1 (TGF-ß1) were observed as indicators of reparative ability and polyneuropathy. All interleukins were determined by ELISA and evaluated spectrophotometrically. Michigan Neuropathy Screening Instrument (MNSI) is performed for neuropathy examination. Patients with diabetes mellitus were divided into 3 groups, according to duration of diabetes mellitus. IL-6 levels correlated with clinical stage of diabetic polyneuropathy at p = 0.025 R = 0.402; with CRP at p = 0.0001, R = 0.784 as well as correlation of CRP and MNSI score (R = 0.500, p = 0.034) in a group of patients with DM lasting up to 10 years. The reparative ability of the body is reduced by physiological age and ages of DM duration. The immune response is weakened in DM additionally. The dual activity of cytokines IL-6 and TGF-ß1 is present in long-duration Diabetes Mellitus.

Evaluation of the Effectiveness of Coronavirus Disease (COVID-19) Therapeutic Protocols Using Inflammatory Markers.

Background: The pathophysiology and therapy of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are a dilemma for scientists and health professionals, and the fact that patients show different symptoms and severity of the clinical picture also contributes to that. Objective: This paper aims to evaluate the effectiveness of therapeutic protocols (the use of immunomodulators) in the treatment of COVID-19 patients of various severity of the clinical picture by monitoring inflammatory markers (ESR and CRP), as well as the impact of the type and number of comorbidities patients had on these markers. Methods: A total of 200 patients with a mild (n=76), moderate (n=70) or severe (n=54) clinical picture was included. Inflammatory markers [ESR (erythrocyte sedimentation rate), CRP (C-reactive protein)] were examined on three occasions: twice during hospitalization and once after hospital discharge. Immunomodulators used intrahospital were corticosteroids (methylprednisolone, dexamethasone, methylprednisolone + dexamethasone), tocilizumab or metenkefalin/tridecactide. Posthospital, patients were taking either methylprednisolone or did not use any immunomodulators. For statistical analysis, SPSS 26.0 and Microsoft Excel 2019 were used, with a level of significance of α=0.05. Nonparametric tests (Kruskal-Wallis and Wilcoxon Signed-Rank) were applied and effect size (ES) was calculated. Results: Three corticosteroid therapies used intrahospital caused a significant decrease in both inflammatory markers, especially in patients with a severe clinical picture, but the ES was the biggest with methylprednisolone + dexamethasone, then dexamethasone, and lastly methylprednisolone. Posthospital, methylprednisolone caused a significant decrease in both inflammatory markers, especially in patients with a severe clinical picture. The most common comorbidity in all patients, as well as in patients with a severe clinical picture, was hypertension. There was no statistically significant impact of the number of comorbidities patients had on ESR and CRP, but the highest number of comorbidities was in patients with a severe clinical picture. Conclusion: The use of immunomodulators, especially methylprednisolone + dexamethasone intrahospital and methylprednisolone posthospital, is justified in most COVID-19 cases as there is a significant correlation between this disease's pathophysiology and the immune response. There is also a positive correlation between the number of comorbidities patients have and the severity of the clinical picture.

The Use of Coagulation Markers to Evaluate the Effectiveness of Coronavirus Disease (COVID-19) Therapeutic Protocols.

Background: Patients infected by coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), display various symptoms and severity of the clinical picture. Thus, the therapy and pathophysiology of this disease are a dilemma for health professionals and scientists. Objective: This paper aims to evaluate the effectiveness of therapeutic protocols (the use of anticoagulants) in the treatment of COVID-19 patients of various severity of the clinical picture by monitoring coagulation markers (PT, INR, aPTT and D-dimer), as well as the impact of the type and number of comorbidities patients had on these markers. Methods: A total of 200 patients with a mild (n=76), moderate (n=70) or severe (n=54) clinical picture was included. Coagulation markers [PT (prothrombin time), INR (international normalized ratio), aPTT (activated partial thromboplastin time), D-dimer] were examined on three occasions: twice during hospitalization and once after hospital discharge. Anticoagulants used intrahospital were fraxiparine, rivaroxaban or unfractionated heparin. Posthospital, patients were taking either rivaroxaban or did not use any anticoagulants. For statistical analysis, SPSS 26.0 and Microsoft Excel 2019 were used, with a level of significance of α=0.05. Nonparametric tests (Kruskal-Wallis, Wilcoxon Signed-Rank and Bonferroni) were applied and effect size (ES) was calculated. Results: Three anticoagulants used intrahospital caused a significant decrease in PT, INR and D-dimer and a significant increase in aPTT, especially in patients with a severe clinical picture, but the ES was the biggest with fraxiparine, then rivaroxaban, and lastly unfractionated heparin. Posthospital, rivaroxaban caused a significant decrease in PT, INR and D-dimer and a significant increase in aPTT, especially in patients with a severe clinical picture. Hypertension was the most common comorbidity in all patients, as well as in patients with a severe clinical picture. There was a statistically significant impact of the number of comorbidities patients had on D-dimer, and none on PT, INR and aPTT, but the highest number of comorbidities was in patients with a severe clinical picture. Conclusion: The use of anticoagulants, especially fraxiparine intrahospital and rivaroxaban posthospital, is justified in most COVID-19 cases as there is a significant correlation between this disease's pathophysiology and the coagulation process. There is also a positive correlation between the severity of the clinical picture and the number of comorbidities patients have.

Application of artificial intelligence for the classification of the clinical outcome and therapy in patients with viral infections: The case of COVID-19.

BACKGROUND: With the end of the coronavirus disease 2019 (COVID-19) pandemic, it becomes intriguing to observe the impact of innovative digital technologies on the diagnosis and management of diseases, in order to improve clinical outcomes for patients. OBJECTIVE: The research aims to enhance diagnostics, prediction, and personalized treatment for patients across three classes of clinical severity (mild, moderate, and severe). What sets this study apart is its innovative approach, wherein classification extends beyond mere disease presence, encompassing the classification of disease severity. This novel perspective lays the foundation for a crucial decision support system during patient triage. METHODS: An artificial neural network, as a deep learning technique, enabled the development of a complex model based on the analysis of data collected during the process of diagnosing and treating 1000 patients at the Tesanj General Hospital, Bosnia and Herzegovina. RESULTS: The final model achieved a classification accuracy of 82.4% on the validation data set, which testifies to the successful application of the artificial neural network in the classification of clinical outcomes and therapy in patients infected with viral infections. CONCLUSION: The results obtained show that expert systems are valuable tools for decision support in healthcare in communities with limited resources and increased demands. The research has the potential to improve patient care for future epidemics and pandemics.

Parameters in predicting the risk of a prolonged hospital stay in patients with acute exacerbation of chronic obstructive pulmonary disease: a single-centre experience.

Aim To identify clinical and laboratory parameters on admission and/or during a hospital stay that would predict prolonged hospital stay in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods A retrospective cross-sectional study was conducted at the Clinic for Pulmonary Diseases and Tuberculosis, Clinical Centre University of Sarajevo for the period 2019-2021 accounting patients admitted due to AECOPD. The need for hospitalization was evaluated according to the current GOLD criteria and certain clinical parameters. Spirometry testing and laboratory analysis were performed for all patients on the day of admission and on the 10th day of hospital stay. Linear regression was used to show the relationship between multiple independent predictor variables and LOS. Results A total of 50 patients were evaluated during their hospital stay due to AECOPD. Median of LOS was 22.02±1.06, with 90% hospital survival rate. Due to AECOPD the median of LOS in the intensive care unit (ICU) was 4±0.68 days with pH<7.35 in 34% of hospitalized patients. According to spirometry classification on the day of admission, 56% of patients were assigned to group 3 and 16% to group 4 with significant improvement identified on spirometry findings on discharge. Platelets on the day of admission were the only statistically significant positive predictors of the length of hospital stay. Conclusion Identifying chronic obstructive pulmonary disease patients at risk of frequent exacerbations and appropriate disease management could reduce the disease burden.

Pregabalin in the Treatment of Peripheral and Central Chronic Neuropathic Pain.

Background: Pregabalin is a first-line therapy of pain with additional positive effects on the states of depression and anxiety that often occur in patients with chronic pain, thus improving their quality of life. Objective: The aim of this study was to demonstrate the efficacy of pregabalin in reducing neuropathic pain and improving quality of life in patients with peripheral and central chronic neuropathic pain in Bosnia and Herzegovina. Also, the aim was to monitor the safety of therapy with pregabalin. Methods: The study included patients with neuropathic pain lasting more than 3 months. Based on the underlying disease, patients were divided into 5 groups: DM-patients with diabetes mellitus, M-patients after stroke, D-patients with lower back pain, MS-patients with multiple sclerosis, and P group-patients with spinal cord injury. During the baseline visit, the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) was used to assess neuropathic pain. During two follow-up visits (1.5 and 3 months after baseline), the 36-Item Short-Form Health Survey (SF 36) was used to assess the effectiveness of therapy on quality of life. The safety of the treatment was evaluated by monitoring the incidence of adverse drug reactions. Results: The study included 125 patients. During treatment with pregabalin, there was a statistically significant reduction in pain intensity in the DM, M, D and MS groups. In group P, the decrease in pain intensity was not statistically significant (p = 0.070). There was a significant improvement in different parameters of the quality of life in all analyzed groups, with the most prominent effects in the DM group. The effectiveness of treatment was rated as "good" and "very good" in more than 70% of subjects in each group. The expected side effects of treatment were recorded in 27.1% of patients in the DM group, in 20.0% in the M group and in 22.2% in the MS group. Unexpected side effects of treatment were observed in one patient (2.1%) in the DM group. Assessment of tolerability of the applied treatment showed "good" and "very good" response in 68.7% of patients in DM group, 73.3% in M group, 74.5% in D group, 88.9% in MS group and 85.8% in P group. Conclusion: Pregabalin is a safe and effective drug in treatment of neuropathic pain of different etiology.

Identification of human genetic variants modulating the course of COVID-19 infection with importance in other viral infections.

Introduction: COVID-19 has been a major focus of scientific research since early 2020. Due to its societal, economic, and clinical impact worldwide, research efforts aimed, among other questions, to address the effect of host genetics in susceptibility and severity of COVID-19. Methods: We, therefore, performed next-generation sequencing of coding and regulatory regions of 16 human genes, involved in maintenance of the immune system or encoding receptors for viral entry into the host cells, in a subset of 60 COVID-19 patients from the General Hospital Tesanj, Bosnia and Herzegovina, classified into three groups of clinical conditions of different severity ("mild," "moderate," and "severe"). Results: We confirmed that the male sex and older age are risk factors for severe clinical picture and identified 13 variants on seven genes (CD55, IL1B, IL4, IRF7, DDX58, TMPRSS2, and ACE2) with potential functional significance, either as genetic markers of modulated susceptibility to SARS-CoV-2 infection or modifiers of the infection severity. Our results include variants reported for the first time as potentially associated with COVID-19, but further research and larger patient cohorts are required to confirm their effect. Discussion: Such studies, focused on candidate genes and/or variants, have a potential to answer the questions regarding the effect of human genetic makeup on the expected infection outcome. In addition, loci we identified here were previously reported to have clinical significance in other diseases and viral infections, thus confirming a general, broader significance of COVID-19-related research results following the end of the pandemic period.

Association of trace element status in COVID-19 patients with disease severity.

Caused by the new SARS-CoV-2 coronavirus, COVID-19 (coronavirus disease 2019) evolves with clinical symptoms that vary widely in severity, from mild symptoms to critical conditions, which can even result in the patient's death. A critical aspect related to an individual response to SARS-CoV-2 infection is the competence of the immune system, and it is well known that several trace elements are essential for an adequate immune response and have anti-inflammatory and antioxidant properties that are of particular importance in fighting infection. Thus, it is widely accepted that adequate trace element status can reduce the risk of SARS-CoV-2 infection and disease severity. In this study, we evaluated the serum levels of Cu, Zn, Se, Fe, I and Mg in patients (n = 210) with clinical conditions of different severity ("mild", "moderate", "severe" and "exitus letalis", i.e., patients who eventually died). The results showed significant differences between the four groups for Cu, Zn, Se and Fe, in particular a significant trend of Zn and Se serum levels to be decreased and Cu to be increased with the severity of symptoms. For Mg and I, no differences were observed, but I levels were shown to be increased in all groups.

Can neutrophil-to-lymphocyte ratio and proatherogenic risk factors improve the accuracy of pneumonia severity index in the prediction of community acquired pneumonia outcome in healthy individuals?

Aim To investigate infl uence of neutrophil-to-lymphocyte ratio (NLR) and proatherogenic risk factors to improve the accuracy of pneumonia severity index (PSI) in the prediction of community acquired pneumonia (CAP) outcome in healthy individuals. Methods A retrospective observational cross-sectional study conducted at the Clinic for Pulmonary Diseases and Tuberculosis "Podhrastovi", University Clinical Centre Sarajevo, included 83 patients with the diagnosis of CAP during the period March 2019-March 2021. Once diagnosed with CAP, PSI score was calculated and according to its value the need for hospital treatment was identifi ed. Patients were divided in two groups: low risk of CAP (PSI <90), and high risk of CAP (PSI> 90). Results The overall average hospital stay was 22.76±10.154 days. In the patients diagnosed with CAP, a positive correlation was established between the following parameters PSI score and age (r=0.670; p<0.01), C-reactive protein-CRP (rho=0.287; p<0.01), leukocytes (rho=0.406; p<0.01), NLR (rho=0.313; p<0.01) and platelet to lymphocyte ratio (PLR) (0.296; p<0.05). CRP, leukocytes, NLR and PLR were statistically signifi cantly higher in patients with high risk of CAP compared to patients with low risk of CAP. Diastolic blood pressure, lymphocytes, eosinophils were signifi cantly lower in patients with high risk of CAP (p<0.05;) compared to patients with low risk of CAP (p<0.01). The optimal cut-off value of NLR for CAP patients was 3.089 with an estimated area under curve (AUC) of 0.664. Conclusion Proatherogenic parameters such as age, systolic blood pressure and leukocytes in combination with neutrophil-lymphocyte count ratio could improve accuracy of the pneumonia severity index in community acquired pneumonia outcome.

IgG N-glycome changes during the course of severe COVID-19: An observational study.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory illness named coronavirus disease 2019 (COVID-19), which is one of the main global health problems since 2019. Glycans attached to the Fc portion of immunoglobulin G (IgG) are important modulators of IgG effector functions. Fc region binds to different receptors on the surface of various immune cells, dictating the type of immune response. Here, we performed a large longitudinal study to determine whether the severity and duration of COVID-19 are associated with altered IgG glycosylation. METHODS: Using ultra-high-performance liquid chromatography analysis of released glycans, we analysed the composition of the total IgG N-glycome longitudinally during COVID-19 from four independent cohorts. We analysed 77 severe COVID-19 cases from the HR1 cohort (74% males, median age 72, age IQR 25-80); 31 severe cases in the HR2 cohort (77% males, median age 64, age IQR 41-86), 18 mild COVID-19 cases from the UK cohort (17% males, median age 50, age IQR 26-71) and 28 mild cases from the BiH cohort (71% males, median age 60, age IQR 12-78). FINDINGS: Multiple statistically significant changes in IgG glycome composition were observed during severe COVID-19. The most statistically significant changes included increased agalactosylation of IgG (meta-analysis 95% CI [0.03, 0.07], adjusted meta-analysis P= <0.0001), which regulates proinflammatory actions of IgG via complement system activation and indirectly as a lack of sialylation and decreased presence of bisecting N-acetylglucosamine on IgG (meta-analysis 95% CI [-0.11, -0.08], adjusted meta-analysis P= <0.0001), which indirectly affects antibody-dependent cell-mediated cytotoxicity. On the contrary, no statistically significant changes in IgG glycome composition were observed in patients with mild COVID-19. INTERPRETATION: The IgG glycome in severe COVID-19 patients is statistically significantly altered in a way that it indicates decreased immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the severity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in COVID-19. FUNDING: This work has been supported in part by Croatian Science Foundation under the project IP-CORONA-2020-04-2052 and Croatian National Centre of Competence in Molecular Diagnostics (The European Structural and Investment Funds grant #KK.01.2.2.03.0006), by the UKRI/MRC (Cov-0331 - MR/V027883/1) and by the National Institutes for Health Research Nottingham Biomedical Research Centre and by Ministry Of Science, Higher Education and Youth Of Canton Sarajevo, grant number 27-02-11-4375-10/21.

Clinical use of an analysis of oxidative stress and IL-6 as the promoters of diabetic polyneuropathy.

Aim To investigate interleukin 6 (IL-6) values depending on duration of diabetes mellitus (DM) and evaluate possible correlation with diabetic polyneuropathy. Methods The research study included 90 patients with DM divided into three groups (30 patients each) according to the duration of DM: group A - patients who had DM for less than 10 years, group B - duration of DM was 10 to 20 years, and group C - patients with DM over 20 years. Control group (K) included 30 healthy participants. Results IL-6 was significantly higher in the healthy control group, 180.318 pg/mL±94.18, than in group A, 47.23pg/ml±34.8, group B, 43.31pg/ml±33.17, and group C, 70.39 pg/ml±59.26 (p=0.0001). All groups had significantly different values of IL-6 between each other (p=0.0001). Level of IL-6 was in correlation with diabetic polyneuropathy in the group A (the youngest participants) (p=0.0001). In other groups there was no significant correlation between IL-6 and diabetic polyneuropathy. Conclusion The level of IL-6 was in correlation with neuropathy among younger patients. A higher level of IL-6 in the control group than in diabetic groups is a sign of stronger inflammatory response among younger and healthy people than in patients with DM.

Chest x-ray resolution after SARS-CoV-2 infection.

Aim To analyse the resolution of chest X-ray findings in relation to laboratory parameters in patients infected with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a two- month followup. Analysis of chest X-ray findings in the first few months after the disease is the main goal of our work. Methods Out of the total of 343 patients chest X-ray findings were followed in 269 patients. Patients were divided into groups according to the severity of findings. D-dimer, inflammatory markers, blood cell count, neutrophil lymphocyte ratio (NLR) were analysed. Chest X-ray was analysed during the hospitalization on the day of admission, on the third, the seventh and the fourteenth day (scoring method was used). After discharge chest X-ray was performed in a two-week follow-up, then after one and two months, and after three months if necessary. Results Incomplete chest X-ray resolution was identified in 24 (39.34%) patients with severe, 27 (22.31 %) patients with moderate and in three (3.91%) patients with mild findings. Statistical significance was established in overall score by comparison between all groups (p<0.001), and in the moderate compared to the mild group (p=0.0051). The difference of NLR in the severe compared to the moderate group was observed (p=0.0021) and in the severe group compared to the mild group (p=0.00013). Conclusion Chest X-ray findings persisted mostly in the severe group followed by the moderate and mild ones. Long-term followup is necessary for the appropriate treatment and prevention of fibrosis, and reduction of symptoms.

Use of chest CT scan scoring system for diagnostic and therapeutic decision making in pleural effusion.

Aim To investigate the usage of chest computed tomography (CT) scan score for improvement in diagnostic and treatment efficacy of repetitive pleural effusion. Methods CT scan scoring system was used as a part of diagnostic procedures in patients with repetitive pleural effusion. Patients with at least two pleurocentesis were included in the study. Chest and abdominal ultrasound, chest x-ray, bronchoscopy, biochemical, microbiological and cytological analysis of pleural fluid specimen were performed for all patients. Results In a two-year period (during 2017-2018) 79 patients were analysed, 27 (34.17%) female and 52 (65.82%) male patients. Malignant pleural diseases were confirmed in 32 cases (40.5%), nonmalignant pleural effusions in 38 (48.1 %) cases, and nine (11.4%) patients rested without exact cause of pleural effusion after two pleurocenteses. Binary regression model showed odds ratio of 1.314; CI 95% 1.119-1.543) (p=0.00088). Confirmed malignancies with pleural effusion were in high correlation with the number of points in CT scan score. Conclusion CT scan scoring system was helpful for diagnostic and treatment decision making in patients with repetitive pleural effusion.

Beta-blocker Use in Moderate and Severe Chronic Obstructive Pulmonary Disease.

INTRODUCTION: The most appropriate choice of pharmacological treatment of heart rhythm disorders occurring in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular comorbidity is often a topic of debate between pulmonologists and cardiologists in clinical practice, although numerous studies and clinical trials have demonstrated evidence to support the use of selective beta-blockers (BBs) in these patients. AIM: To examine the difference in the number of exacerbations in patients treated with a combination of verapamil and digoxin or BB alone in patients with different COPD stages. PATIENTS AND METHODS: The study included 68 patients (n = 68) diagnosed with COPD who were followed-up during a 12-month period, and the number of exacerbations were analyzed. The patients were divided into two groups according to the stage of COPD: GOLD II (moderate), and GOLD III (severe), and in each group a subdivision was established in relation to the use of either a combination of verapamil and digoxin or the use of BBs alone in pharmacological treatment. The inclusion criteria for patients were defined as following: a) established diagnosis of COPD according to present or deteriorated relevant clinical symptoms and signs, b) the ejection fraction (EF) of a left ventricle (LV) >35%, and c) spirometric cut-points classified as GOLD II (FEV1 / FVC <0.7, FEV1 predicted 50-80%), or GOLD III (FEV1/FVC <0.7, FEV1 predicted 30-50%) stage of the COPD. The exclusion criteria were EF of LV <35% and a lethal outcome during a follow-up period (2 patients were encountered). Exacerbation was defined as functional deterioration of the COPD symptoms verified by spirometric functional testing, frequency of hospitalizations according to GOLD stage assignment or verified clinical symptoms deterioration. RESULTS: Regardless the pharmacological treatment, there is a statistically significant increase in the number of COPD exacerbations, in a 12-month period follow-up, in the GOLD III group (severe) compared to the GOLD II group (moderate). In the group of patients taking verapamil and digoxin, a two-tailed t-test was used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.01, and 2. In the group of patients taking BBs, a two-tailed t-test was also used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.003). Within the COPD GOLD II stage group, there appears to be no statistically significant difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 24) and the patients taking BBs alone (n = 15), although, in patients taking BBs alone, there appears to be a trend towards a decrease in the exacerbations compared to the number of exacerbations in patients taking verapamil and digoxin (p = 0.007). Within the COPD GOLD III stage group, there is no difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 20), and the patients taking BBs alone (n = 9), as analyzed by a two-tailed t-test, p = 0.577. CONCLUSION: Use of selective BBs in the treatment of cardiovascular comorbidity in patients with COPD represents a far better choice of pharmacological approach in the treatment of patients diagnosed with COPD GOLD II (moderate) stage.

Association of IRS1 genetic variants with glucose control and insulin resistance in type 2 diabetic patients from Bosnia and Herzegovina.

Background Previous studies reported conflicting results regarding association of insulin receptor substrate 1 (IRS1) gene variation with type 2 diabetes (T2D) and insulin resistance (IR) in different ethnic groups. We examined the association of rs7578326, rs2943641, and rs4675095 in the IRS1 gene with T2D and related traits in a population from Bosnia and Herzegovina, which is one of the European countries with the highest T2D prevalence of 12.5%. Methods Our study included 390 T2D patients and 252 control subjects. Biochemical parameters, including fasting glucose (FG), fasting insulin (FI), homeostasis model assessment insulin resistance index (HOMA-IR), and HbA1c were measured in all participants. Genotyping analysis was performed by Mass Array Sequenom iPlex platform. Results Our results demonstrated that rs7578326 and rs4675095 variants were associated with increased FG levels. The rs7578326 was also associated with higher FI, HOMA-IR (B = 0.08, 95% CI [0.01, 0.15], padd = 0.025; B = 0.079, 95% CI [0.006, 0.150], padd = 0.033, respectively) in T2D, and with HbA1c (B = 0.034, 95% CI [0.003, 0.065], pdom = 0.035) in non-drug-treated T2D. In contrast, rs2943641 C allele was associated with lower FG levels in control subjects (B = -0.17, 95% CI [-0.03, -0.002], padd = 0.030) and HbA1c (B = 0.03, 95% CI [0.002, 0.06], pdom = 0.040) in non-drug-treated T2D. Conclusions We report the association between common variants in IRS1 gene with insulin resistance, glucose, and HbA1c levels in Bosnia and Herzegovina's population.

Association of FTO Gene Variant (rs8050136) with Type 2 Diabetes and Markers of Obesity, Glycaemic Control and Inflammation.

BACKGROUND: FTO, a gene recently discovered in genomewide associated studies for type 2 diabetes mellitus (T2D), play an important role in the management of energy homeostasis, nucleic acid demethylation and regulation of body fat mass by lipolysis. The aim of this study was to analyze the association of FTO rs8050136 A>C genetic variant with clinical and biochemical parameters of T2D in the population of West Balkan region (Bosnians and Herzegovinians and Kosovars). METHODS: The study included 638 patients with T2D and prediabetes and 360 healthy controls of both genders, aged from 40 to 65 years. Patients were recruited at the Clinical Centre University of Sarajevo, University Hospital of Clinical Centre in Banja Luka, General Hospital in Tesanj and Health Centre in Prizren. Genotyping of analyzed FTO polymorphism rs8050136 A>C was performed by qPCR allelic discrimination. RESULTS: Genotype frequencies of the analyzed polymorphism were comparable between patients with T2D, prediabetic patients, and healthy population. Logistic regression analyses didn't show significant association of FTO rs8050136 A allele with increased risk of T2D. However, risk A allele was significantly associated with higher levels of HbA1c, insulin, HOMA-IR index, diastolic blood pressure, and inflammatory markers (fibrinogen and leukocytes) as well as showed tendency of association with increased values of obesity markers (BMI, waist and hip circumference). CONCLUSIONS: Results of our study showed a significant association of FTO genetic variant rs8050136 A>C with the major markers of insulin resistance, obesity and inflammation, opening new avenues for solving many unclear questions in the pathogenesis of T2D.

Diagnostic and prognostic value of procalcitonin in patients with sepsis.

Aim To investigate predictive value of procalcitonin in diagnosis of sepsis in predicting positive blood culture, and possibility to predict final outcome in septic patients. Method This prospective study involved 106 hospitalized patients who met two or more criteria for systemic inflammatory response syndrome (SIRS). In comparison to Sepsis Related Organ Failure Assessment score (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II score procalcitonin (PCT), C-reactive protein and lactate levels were used to predict final outcome in septic patients (recorded as 28-day survival or non-survival). Using Receiver operating characteristic (ROC) curve the area under the curve (AUC) was calculated for diagnostic value and accuracy of different parameters with the best sensitivity and specificity for given cut-off values. Result Fifty-two out of 82 patients with documented sepsis had positive blood culture. Procalcitonin showed the best predictive value for both diagnosis of sepsis and bacteraemia with the cut-off value of 0.57 ng/mL (AUC 0.99) and 4.68 ng/mL (AUC 0.94), respectively. Serum lactate level showed the best 28-day mortality predictive value with the cut-off value of 3.25 mmol/L (AUC 0.95), and procalcitonin with the cut-off value of 15.05 ng/mL (AUC 0.92), followed by SOFA (AUC 0.92), CRP (AUC 0.84) and APACHE II score (AUC 0.83). Conclusion Monitoring of PCT in SIRS-positive patients raises possibility to distinguish between patients with sepsis and those with non-infectious SIRS. A significant correlation between PCT and SOFA, and APACHE II score in non-surviving septic patients indicates that PTC combined with clinical score could be useful for assessing severity of infection.